Prenatal exposure to methadone or buprenorphine impairs cognitive performance in young adult rats

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α1-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α1-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α1-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively. We also determined the α1-adrenoceptor density in whole hypothalamus and the expression levels of α1A-adrenoceptor mRNA in the PVN. The results showed that: (i) agonists microinjection increased systolic blood pressure and heart rate in normotensive eutrophic rats, but not in prenatally malnourished subjects; (ii) antagonists microinjection reduced hypertension and tachycardia in undernourished rats, but not in eutrophic controls; (iii) in undernourished animals, antagonist administration to one nuclei allowed the agonists recover full efficacy in the complementary nucleus, inducing hypertension and tachycardia; (iv) early undernutrition did not modify the number of α1-adrenoceptor binding sites in hypothalamus, but reduced the number of cells expressing α1A-adrenoceptor mRNA in the PVN. These results support the hypothesis that systolic pressure and heart rate are increased by tonic reciprocal paraventricular–coerulear excitatory interactions in prenatally undernourished young-adult rats.

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Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice

International Journal of Retina and Vitreous ◽

10.1186/s40942-021-00314-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Paulo Roberto Arruda Zantut ◽

Mariana Matera Veras ◽

Sarah Gomes Menezes Benevenutto ◽

Angélica Mendonça Vaz Safatle ◽

Ricardo Augusto Pecora ◽

...

Keyword(s):

Young Adult ◽

Light Microscopy ◽

Prenatal Exposure ◽

Structural Changes ◽

Volume Fraction ◽

Clinical Care ◽

Retinal Layer ◽

Exposed Population ◽

The Central Nervous System ◽

The Impact

Abstract Background Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.

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Responsiveness to cocaine challenge in adult rats following prenatal exposure to cocaine

Psychopharmacology ◽

10.1007/bf02244870 ◽

1994 ◽

Vol 116 (1) ◽

pp. 45-55 ◽

Cited By ~ 25

Author(s):

Charles J. Heyser ◽

Lavanya Rajachandran ◽

Norman E. Spear ◽

Linda Patia Spear

Keyword(s):

Prenatal Exposure ◽

Adult Rats

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Stimulus-specific adaptation in auditory thalamus of young and aged awake rats

Journal of Neurophysiology ◽

10.1152/jn.00403.2013 ◽

2013 ◽

Vol 110 (8) ◽

pp. 1892-1902 ◽

Cited By ~ 17

Author(s):

Ben D. Richardson ◽

Kenneth E. Hancock ◽

Donald M. Caspary

Keyword(s):

Young Adult ◽

Auditory Cortex ◽

Brown Norway ◽

Oddball Paradigm ◽

Adult Rats ◽

Specific Adaptation ◽

Auditory Thalamus ◽

Gating Mechanism ◽

Medial Geniculate ◽

Awake Rats

Novel stimulus detection by single neurons in the auditory system, known as stimulus-specific adaptation (SSA), appears to function as a real-time filtering/gating mechanism in processing acoustic information. Particular stimulus paradigms allowing for quantification of a neuron's ability to detect novel or deviant stimuli have been used to examine SSA in the inferior colliculus, medial geniculate body (MGB), and auditory cortex of anesthetized rodents. However, the study of SSA in awake animals is limited to auditory cortex. The present study used individually advanceable tetrodes to record single-unit responses from auditory thalamus (MGB) of awake young adult and aged Fischer Brown Norway (FBN) rats to 1) examine the presence of SSA in the MGB of awake rats and 2) determine whether SSA is altered by aging in MGB. MGB single units in awake FBN rats displayed SSA in response to two stimulus paradigms: the oddball paradigm and a random blocked/interleaved presentation of a set of frequencies. SSA levels were modestly, but nonsignificantly, increased in the nonlemniscal regions of the MGB and at lower stimulus intensities, where 27 of 57 (47%) young adult MGB units displayed SSA. The present findings provide the initial description of SSA in the MGB of awake rats and support SSA as being qualitatively independent of arousal level or anesthetized state. Finally, contrary to previous studies in auditory cortex of anesthetized rats, MGB units in aged rats showed SSA levels indistinguishable from SSA levels in young adult rats, suggesting that SSA in MGB was not impacted by aging in an awake preparation.

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Differential effects of targeted tongue exercise and treadmill running on aging tongue muscle structure and contractile properties

Journal of Applied Physiology ◽

10.1152/japplphysiol.01370.2012 ◽

2013 ◽

Vol 114 (4) ◽

pp. 472-481 ◽

Cited By ~ 28

Author(s):

Heidi Kletzien ◽

John A. Russell ◽

Glen E. Leverson ◽

Nadine P. Connor

Keyword(s):

Young Adult ◽

Exercise Group ◽

Contractile Properties ◽

Treadmill Running ◽

Brown Norway ◽

Middle Aged ◽

Adult Rats ◽

Tongue Muscle ◽

Muscle Structure ◽

Old Rats

Age-associated changes in tongue muscle structure and strength may contribute to dysphagia in elderly people. Tongue exercise is a current treatment option. We hypothesized that targeted tongue exercise and nontargeted exercise that activates tongue muscles as a consequence of increased respiratory drive, such as treadmill running, are associated with different patterns of tongue muscle contraction and genioglossus (GG) muscle biochemistry. Thirty-one young adult, 34 middle-aged, and 37 old Fischer 344/Brown Norway rats received either targeted tongue exercise, treadmill running, or no exercise (5 days/wk for 8 wk). Protrusive tongue muscle contractile properties and myosin heavy chain (MHC) composition in the GG were examined at the end of 8 wk across groups. Significant age effects were found for maximal twitch and tetanic tension (greatest in young adult rats), MHCIIb (highest proportion in young adult rats), MHCIIx (highest proportion in middle-aged and old rats), and MHCI (highest proportion in old rats). The targeted tongue exercise group had the greatest maximal twitch tension and the highest proportion of MHCI. The treadmill running group had the shortest half-decay time, the lowest proportion of MHCIIa, and the highest proportion of MHCIIb. Fatigue was significantly less in the young adult treadmill running group and the old targeted tongue exercise group than in other groups. Thus, tongue muscle structure and contractile properties were affected by both targeted tongue exercise and treadmill running, but in different ways. Studies geared toward optimizing dose and manner of providing targeted and generalized tongue exercise may lead to alternative tongue exercise delivery strategies.

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